Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Data is available online

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other:
Principles of method if other than guideline:
Details of guidelines not mentioned in the publication
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Methyl N Methylanthranilate (MNMA)
Radiolabelling:
no

Test animals

Species:
other: Guinea pigs (Liver microsomes & cytosol)
Strain:
Hartley
Sex:
male

Administration / exposure

Route of administration:
other: in-vitro hence not applicable
Vehicle:
other: in-vitro hence not applicable
Details on exposure:
MNMA was incubated with guinea pigs liver microsomes (5 µg protein) or cytosol (50 µg protein) in sodium-potassium phosphate buffer 38 mM (pH 7.4) in a final volume of 260 µl. The mixture was incubated at 37oC for 10 mins, and the reaction was terminated by the addition of acetonitrile 200 µl containing methyl p-methoxybenzoate (0.20 µg) as an internal standard. After the removal of protein by centrifugation, 50 µl of the supertanant was injected onto a High Performance Liquid Chromatography (HPLC) system.
Duration and frequency of treatment / exposure:
10 mins
Doses / concentrations
Remarks:
Doses / Concentrations:
1000 µM
No. of animals per sex per dose:
Not applicable
Control animals:
no

Results and discussion

Main ADME results
Type:
metabolism
Results:
MNMA was hydrolyzed by guinea pigs liver microsomes to produce N-Methyl Anthranilic acid. MNMA was also N-Demthylated by Guinea pigs liver microsomes & cytosol to form anthranilic acid (AA).

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Not Applicable
Details on distribution in tissues:
Not Applicable
Details on excretion:
Not Applicable

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
N-Methyl Anthranilic acid &
Anthranilic acid (AA)

Any other information on results incl. tables

MNMA was hydrolyzed byguinea pigs liver microsomes to produceN-Methyl Anthranilic acid.MNMA was also N-Demthylated byGuinea pigs liver microsomes & cytosol to form anthranilic acid (AA).

Kinetic analysis indicated that Vmax/Km values were 7.4 fold higher in microsomes than in cytosol

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): low bioaccumulation potential based on study results
In vitro study of hepatic metabolism of Methyl N Methylanthranilate in guinea pigs liver microsomes was conducted wherein the kinetic analysis indicated that Vmax/Km values were 7.4 fold higher in microsomes than in cytosol. Vmax/Km values reflect the intrinsic clearance potential after hydrolysis and thus the bio-accumulation potential of Methyl N Methylanthranilate (MNMA) is expected to be low.
Executive summary:

In vitro study of hepatic metabolism of Methyl N Methylanthranilate in guinea pigs liver microsomes was conducted wherein the kinetic analysis indicated that Vmax/Km values were 7.4 fold higher in microsomes than in cytosol. Vmax/Km values reflect the intrinsic clearance potential after hydrolysis and thus the bio-accumulation potential ofMethyl N Methylanthranilate (MNMA)is expected to be low.